Application method and system of modified glutinous rice flour in medicine tablets

Abstract

The invention discloses an application method and system of modified glutinous rice flour in medicine tablets, and relates to the technical field of biological medicines.The method comprises the steps that high-amylopectin glutinous rice flour is subjected to moist heat, acidolysis, oxidation, crosslinking or enzymatic modification, and the gelatinization temperature, viscosity, water absorption expansion rate and disintegration time limit of the high-amylopectin glutinous rice flour are regulated and controlled; matching corresponding modification process and functional parameters according to the tablet type; the modified glutinous rice flour is mixed with the main medicine according to the proportion of 5%-50%, and dry method / wet method granulation or direct tabletting molding is adopted; the system comprises a raw powder pretreatment unit, a multi-chamber modification treatment unit, a post-treatment unit, a function judgment module, an ingredient mixing unit and an intelligent tabletting unit. The single modified glutinous rice flour integrates the three functions of filling, bonding and disintegration, the formability, disintegration performance or slow release effect of the tablet is remarkably improved, the cost is reduced by 30% or above, and the tablet has good safety and batch-to-batch consistency.

Description

TECHNICAL FIELD

[0001] The application relates to the technical field of biological medicine, and particularly relates to an application method and system of modified glutinous rice powder in medicine tablets. BACKGROUND

[0002] As the most widely used solid dosage form in clinical application, the preparation process of medicine tablets highly depends on the functional support of excipients. Although traditional medicinal excipients such as microcrystalline cellulose, lactose, pregelatinized starch and cross-linked sodium carboxymethyl cellulose have certain performances in filling, bonding or disintegration, they generally have problems such as limited source, high cost, single function and poor compatibility with traditional Chinese medicine extract. Especially in the field of traditional Chinese medicine tablets, the extract itself has characteristics such as high viscosity, high hygroscopicity and complex composition, which often leads to defects such as sticking, loose tablets, slow disintegration or uneven dissolution in the tabletting process. The existing excipient system cannot simultaneously meet the comprehensive requirements of formability, stability and release performance, and it is urgent to develop a new type of natural excipient with safety, multifunctionality and process adaptability.

[0003] Among them, the main component of glutinous rice powder is amylopectin, which has good thermoplasticity, viscoelasticity and biocompatibility, and meets the principle of "medicinal food homology". It has a long application basis in food and traditional medicine. However, the original glutinous rice powder without modification has inherent defects such as high gelatinization temperature, cold water insolubility, poor flowability and uncontrollable function, which cannot directly meet the fine requirements of modern tablets on the rheological property, compressibility and release characteristics of excipients. Although some studies attempt to use starch substances as tablet excipients, most focus on the single modification of corn or potato starch, lack of systematic process design for the structural characteristics of waxy starch, and no precise mapping relationship between the modification type and the function of the dosage form is established, which makes it difficult to achieve stable and repeatable process performance in actual production.

[0004] In the prior art, the selection of excipients often adopts the "multi-component compounding" strategy, that is, adding fillers, binders and disintegrants to meet different functional requirements. This mode not only increases the complexity of the prescription and the difficulty of quality control, but also may cause stability risks due to the interaction between excipients. In addition, the conventional modification process of starch often uses high temperature and high pressure or strong chemical reagents, which easily destroys the molecular structure of starch and introduces impurities, which does not meet the development trend of green pharmaceutical and natural medicine preparation. In specific dosage forms such as traditional Chinese medicine extract tablets, dispersible tablets or sustained-release tablets, the existing excipient system still cannot meet the requirements of formability, rapid disintegration or controlled release under high drug loading. SUMMARY

[0005] The purpose of the application is to provide an application method and system of modified glutinous rice powder in medicine tablets, so as to solve the problems of various excipients, poor compatibility, high cost and difficulty in forming traditional Chinese medicine extract tablets.

[0006] To solve the above technical problems, the present application provides the following technical solutions: In one aspect, a method for applying modified waxy rice powder in a pharmaceutical tablet, comprising: Step S1, obtaining unmodified raw waxy rice powder, and performing modification treatment on the raw waxy rice powder. The amylopectin content of the raw waxy rice powder is not less than 95%, the moisture content is not higher than 10%, and the particle size D90 is not greater than 100 microns. The modification treatment is selected from any one of the following ways: wet heat treatment, acid hydrolysis treatment, oxidation treatment, crosslinking treatment or enzyme catalytic modification treatment; wherein the wet heat treatment conditions are: treating at a relative humidity of 75% to 85% and a temperature of 110°C to 130°C for 1 to 3 hours; the acid hydrolysis treatment uses a hydrochloric acid solution with a concentration of 0.5% to 2%, and reacts at a temperature of 40°C to 60°C for 30 to 120 minutes; the oxidation treatment uses a sodium hypochlorite solution with a concentration of 0.1% to 0.5%, and reacts at a pH of 8.5 to 9.5 and a temperature of 30°C to 50°C for 1 to 2 hours; the crosslinking treatment uses sodium trimetaphosphate as a crosslinking agent, with a dosage of 0.3% to 1.5% of the dry weight of the waxy rice powder, and reacts at a pH of 9 to 10 and a temperature of 45°C to 55°C for 2 to 4 hours; the enzyme catalytic modification treatment uses a pullulanase, with an enzyme addition amount of 0.1% to 0.5% of the dry weight of the waxy rice powder, and reacts at a pH of 5.5 to 6.5 and a temperature of 55°C to 65°C for 4 to 8 hours; Step S2, drying, crushing and sieving the modified waxy rice powder to obtain a modified waxy rice powder product, wherein the gelatinization onset temperature of the modified waxy rice powder product is 60°C to 80°C, the peak viscosity is 300 to 1,500 centipoise, the water absorption expansion rate is not less than 200%, and the disintegration time in simulated gastric fluid is not more than 15 minutes; Step S3, determining the functional role of the modified waxy rice powder according to the type of the target pharmaceutical tablet, if the target tablet is an immediate-release tablet, selecting the modified waxy rice powder obtained by wet heat treatment or acid hydrolysis treatment, and controlling the disintegration time to be 5 to 12 minutes; if the target tablet is a sustained-release tablet, selecting the modified waxy rice powder obtained by crosslinking treatment or oxidation treatment, and controlling the dissolution rate in simulated intestinal fluid within 24 hours to be not less than 70% and the disintegration time to be greater than 30 minutes; if the target tablet is a traditional Chinese medicine extract tablet, selecting the modified waxy rice powder obtained by enzyme catalytic modification treatment, and controlling the viscosity index to be 80 to 120, which can effectively adjust the viscosity of the extract and improve the tablet forming rate; Step S4, mixing the modified waxy rice powder with the main drug and other necessary excipients according to a predetermined proportion, wherein the proportion of the modified waxy rice powder in the total mass of the tablet is 5% to 50%; Step S5, the mixture is pressed into a tablet by dry granulation, wet granulation or direct compression process, the tabletting pressure is controlled at five to fifteen thousand Newton, the tablet hardness is not less than fifty Newton, and the friability is less than 0.8%.

[0007] In another aspect, a modified waxy rice powder application system in a pharmaceutical tablet includes: A native waxy rice powder pretreatment unit for receiving and screening native waxy rice powder meeting the requirements of amylopectin content, moisture content, and particle size; A modification treatment unit including multiple independent reaction chambers respectively configured with temperature control, pH adjustment, stirring, and feeding devices for performing heat-moisture treatment, acid hydrolysis treatment, oxidation treatment, cross-linking treatment, or enzyme catalytic modification treatment, each reaction chamber having an independent parameter control system capable of setting and maintaining specific temperature, humidity, pH value, reaction time, and reagent concentration; A post-treatment unit including a fluidized bed dryer, a universal pulverizer, and a vibrating sieve machine in sequence for drying, pulverizing, and particle size grading the modified product to obtain modified waxy rice powder finished product with D90 of thirty to eighty microns; A function determination module with a built-in database storing key performance parameter thresholds corresponding to different modification processes, including gelatinization temperature interval, viscosity range, water absorption swelling rate lower limit, and disintegration time upper limit, which automatically matches the optimal modification process path and outputs corresponding modified waxy rice powder specification parameters according to the input tablet type instruction; A batching and mixing unit equipped with a high-shear mixer for uniformly mixing the main drug, modified waxy rice powder, and other excipients in proportion by mass, with a mixing time of five to fifteen minutes and a rotation speed of two hundred to six hundred revolutions per minute; A tablet compression unit using a rotary tablet press equipped with a pressure feedback control system for real-time monitoring and adjusting the die pressure to ensure that the tablet hardness and friability meet the preset standards.

[0008] As an embodiment of the present application, the gelatinization characteristics of the modified waxy rice powder are determined by a rapid viscosity analyzer with a sample concentration of 10%, a temperature rise rate of 12°C per minute, a temperature holding time of five minutes after rising from 50°C to 95°C, and a temperature drop rate of 12°C per minute to 50°C, and the peak viscosity, disintegration viscosity, and retrogradation value are recorded.

[0009] As an embodiment of the present application, the disintegration performance of the modified waxy rice powder is determined by the disintegration time limit test method specified in Chinese Pharmacopoeia 0921, with nine hundred milliliters of artificial gastric juice as the medium, a temperature of thirty-seven degrees Celsius plus or minus zero point five degrees Celsius, and the time required for complete disintegration of all samples being recorded.

[0010] As an embodiment of the present application, in the preparation of traditional Chinese medicine extract tablets, the main medicine is traditional Chinese medicine extract with water content not less than 30%, the mass ratio of the traditional Chinese medicine extract to modified waxy rice flour is 1:0.5 to 1:2, the rest angle of the mixed material is not more than 45 degrees, and the compression formability index of the mixed material is not less than 80%.

[0011] As an embodiment of the present application, the modified waxy rice flour simultaneously assumes the functions of filler, binder and disintegrant in the tablet, and does not need to additionally add microcrystalline cellulose, hydroxypropyl methyl cellulose or cross-linked sodium carboxymethyl cellulose.

[0012] Further, each reaction chamber in the modification treatment unit is provided with an online near-infrared spectrum monitoring module for real-time acquisition of the change characteristics of the molecular structure of waxy rice flour during the reaction, and the reaction is automatically terminated when the branch length distribution of amylopectin reaches the target interval, i.e., the proportion of DP6 to DP12 is not less than 60%.

[0013] Further, a dynamic proportion adjustment interface is arranged between the function determination module and the ingredient mixing unit, and when the fluidity or hygroscopicity of the main medicine exceeds the preset threshold, the system automatically increases the addition proportion of the modified waxy rice flour, which is not more than 50% of the total mass of the tablet.

[0014] Further, the tablet compression forming unit is provided with a tablet appearance detection subsystem, a high-resolution industrial camera is used to perform full-circle scanning on the surface of the tablet, defects such as cracked tablets, loose tablets, pitting or color difference are identified, and unqualified products are automatically removed.

[0015] Compared with the prior art, the present application has the following beneficial technical effects: The present application realizes the integrated application of a single natural auxiliary material in the functions of filling, binding and disintegration in a drug tablet by systemically designing the preparation process and application parameter system of the modified waxy rice flour. For the problem of difficult granulation and tablet sticking and sticking caused by high viscosity of traditional Chinese medicine extract tablets, the enzyme-catalyzed modified waxy rice flour provided by the present application significantly improves the fluidity and compressibility of the material, increases the hardness of the tablet by more than 20%, and reduces the friability to less than 0.5%. For immediate-release tablets, the disintegration time of the waxy rice flour modified by wet heating or acidolysis in simulated gastric juice is shortened to less than 8 minutes, which is better than the 12 minutes of traditional corn starch auxiliary materials; for sustained-release tablets, the three-dimensional network structure formed by the cross-linked or oxidized modified waxy rice flour effectively delays drug release, maintains a stable dissolution curve within 24 hours, and avoids the burst effect. In addition, the present application discards synthetic or semi-synthetic auxiliary materials such as microcrystalline cellulose and lactose, reduces the raw material cost by more than 30%, and because the waxy rice flour is a homologous material of medicine and food, it has no toxic side effects and is highly compatible with traditional Chinese medicine ingredients, significantly improving the safety and patient compliance of the preparation. The whole system realizes the precise matching of auxiliary material performance and tablet demand through the cooperation of the function determination module and the online monitoring device, ensuring batch consistency and process robustness. Attached Figure Description

[0016] Figure 1 This is a schematic diagram of the overall technical solution architecture of the application method and system of modified glutinous rice flour in pharmaceutical tablets proposed in this invention; Figure 2 This is a schematic diagram of the core principle framework of the modified glutinous rice flour multifunctional integrated regulation and tablet type adaptation proposed in this invention. Detailed Implementation

[0017] The features and exemplary embodiments of various aspects of the present invention will now be described in detail. To make the objectives, technical solutions, and advantages of the present invention clearer, the present invention will be further described in detail below with reference to the accompanying drawings and specific embodiments. It should be understood that the specific embodiments described herein are merely intended to explain the present invention and not to limit the present invention. For those skilled in the art, the present invention can be practiced without some of these specific details. The following description of the embodiments is merely to provide a better understanding of the present invention by illustrating examples of the invention. Example

[0018] This invention provides a method and system for applying modified glutinous rice flour in pharmaceutical tablets. The core of this method lies in controlling the physicochemical properties of glutinous rice flour through a specific modification process, enabling it to simultaneously achieve the triple functions of filling, binding, and disintegration within a single excipient system, and dynamically adapting its functional role according to the target tablet type. The following detailed description of the method steps and system structure further illustrates this invention.

[0019] The method begins with step S1, obtaining unmodified virgin glutinous rice flour. This virgin glutinous rice flour must meet three basic requirements: amylopectin content of not less than 95%, moisture content of not more than 10%, and particle size D90 of not more than 100 micrometers. Amylopectin, as the main component of glutinous rice flour, ensures good thermal stability and plasticity during subsequent modification; low moisture content prevents microbial growth or clumping during storage or processing; and the defined particle size distribution ensures uniformity and flowability during subsequent mixing and tableting. The virgin glutinous rice flour is screened using a sieving device, employing a standard sieve with a 100-micrometer aperture for initial screening to remove coarse impurities. The amylopectin content of each batch of samples is then rapidly determined using a near-infrared spectroscopy. Only samples meeting the threshold requirements can proceed to the next step.

[0020] Subsequently, step S1 is continued: the original glutinous rice powder is subjected to a modification treatment. The modification treatment is performed from one of five preset modes, which are wet heat treatment, acid hydrolysis treatment, oxidation treatment, crosslinking treatment or enzyme catalytic modification treatment. Each treatment mode corresponds to different reaction conditions and functional orientation. The wet heat treatment is carried out in a sealed constant temperature and humidity reaction chamber, with the relative humidity controlled at 75% to 85%, the temperature set at 110°C to 130°C, and the duration of 1 to 3 hours. Under these conditions, the starch granules inside the glutinous rice powder undergo partial gelatinization and recrystallization, forming a porous and loose structure, significantly improving its water absorption and swelling capacity and disintegration performance, suitable for the preparation of immediate-release tablets. The acid hydrolysis treatment uses a hydrochloric acid solution with a concentration of 0.5% to 2%, and the reaction is carried out in a water bath at 40°C to 60°C for 30 to 120 minutes. Acid molecules penetrate into the interior of starch granules, selectively hydrolyze α-1,6 glycosidic bonds, reduce molecular weight and weaken intermolecular hydrogen bonding, thereby reducing viscosity and increasing dissolution rate, also used in the context of immediate-release tablets. The oxidation treatment uses a sodium hypochlorite solution with a concentration of 0.1% to 0.5%, and the reaction is carried out at pH 8.5 to 9.5 and 30°C to 50°C for 1 to 2 hours. Hypochlorite ions oxidize the hydroxyl groups of starch to form carboxyl groups, introducing negative charges, enhancing hydrophilicity and swelling capacity, and forming a partial crosslinking structure to delay dissolution, suitable for sustained-release tablets. The crosslinking treatment uses sodium trimetaphosphate as the crosslinking agent, with a dosage of 0.3% to 1.5% of the dry weight of the glutinous rice powder, and the reaction is carried out at pH 9 to 10 and 45°C to 55°C for 2 to 4 hours. Sodium trimetaphosphate reacts with the hydroxyl groups on the starch molecules to form a three-dimensional network skeleton, significantly inhibiting the swelling rate and drug burst, and is specifically used for sustained-release tablets. The enzyme catalytic modification treatment uses pullulanase, with an enzyme addition amount of 0.1% to 0.5% of the dry weight of the glutinous rice powder, and the reaction is carried out at pH 5.5 to 6.5 and 55°C to 65°C for 4 to 8 hours. Pullulanase specifically hydrolyzes the short chains outside the amylopectin, i.e. DP6 to DP12, moderately reduces the branching density, optimizes the viscoelasticity and compressibility, and is particularly suitable for the molding requirements of high-viscosity traditional Chinese medicine extract tablets.

[0021] During the modification reaction process, each reaction chamber is equipped with an online near-infrared spectrum monitoring module to collect the absorption spectrum of the glutinous rice powder in the 1100 to 2500 nm wave band in real time. By analyzing the characteristic peak shift and intensity change, the amylopectin branching length distribution is inverted. When the DP6 to DP12 fragment proportion reaches not less than 60% of the target interval, the control system automatically terminates the reaction process, ensuring that the modification degree is accurately controllable. This mechanism avoids the batch-to-batch differences caused by relying on fixed time in traditional end-point determination, and realizes process closed-loop control at the molecular scale.

[0022] After modification, step S2 is performed: the modified waxy rice flour is dried, crushed and sieved to obtain modified waxy rice flour finished product. Fluidized bed dryer is used for drying, with inlet air temperature set to 70°C and material residence time of 30 minutes to reduce moisture content to below 3%. Subsequently, mechanical crushing is performed by universal crusher, with rotor speed of 3000 rpm and crushing time of 5 minutes. The crushed product is classified by a vibrating screen classifier, with screen mesh size of 80 μm and 30 μm, and fine powder with D90 between 30 μm and 80 μm is collected as the final product. This particle size range takes into account the flowability and compressibility, avoiding excessive fineness leading to dust flying or excessive coarseness affecting the surface smoothness of the tablets. The obtained modified waxy rice flour finished product needs to meet four key performance indicators: the gelatinization onset temperature is 60-80°C, the peak viscosity is 300-1500 cP, the water absorption swelling rate is not less than 200%, and the disintegration time in simulated gastric juice is not more than 15 minutes. The gelatinization properties are determined by a rapid viscosity analyzer, with sample concentration of 10%, heating rate of 12°C / min, temperature rise from 50°C to 95°C for 5 minutes, then cooling at the same rate to 50°C, recording the viscosity curve throughout the process, and extracting the peak viscosity, disintegration viscosity and retrogradation value. The disintegration performance is determined according to the method specified in Chinese Pharmacopoeia 0921, with 900 ml artificial gastric juice as the medium, temperature maintained at 37°C ± 0.5°C, and the time required for complete disintegration of all samples is recorded.

[0023] Then step S3 is performed: the functional role of the modified waxy rice flour is determined according to the type of the target drug tablet. If the target tablet is an immediate-release tablet, the modified waxy rice flour obtained by wet heat treatment or acid hydrolysis treatment is selected, with disintegration time strictly controlled within 5-12 minutes. Such modified waxy rice flour has loose or porous structure, rapidly absorbs water and swells upon contact with water, and breaks down to promote tablet disintegration within a short time, releasing the main drug. If the target tablet is a sustained-release tablet, the modified waxy rice flour obtained by cross-linking treatment or oxidation treatment is selected, with dissolution rate not less than 70% within 24 hours in simulated intestinal juice and disintegration time greater than 30 minutes. The network structure formed by cross-linking or oxidation limits the water penetration rate, allowing the drug to be released slowly by diffusion or erosion mechanism, avoiding sudden increase in blood drug concentration. If the target tablet is a traditional Chinese medicine extract tablet, the modified waxy rice flour obtained by enzyme catalytic modification treatment is selected, with viscosity index of 80-120. The viscosity index is determined by a rotary viscometer at 25°C, shear rate of 100 / s, reflecting the cohesive force and plastic deformation ability of the material during tabletting. Enzyme-modified waxy rice flour can effectively adsorb free water and sticky polysaccharides in traditional Chinese medicine extract, reducing the overall material stickiness and improving flowability and compressibility. The material after mixing has a rest angle not greater than 45° and a compression formability index not less than 80%, ensuring no sticking, cracking or other phenomena during tabletting.

[0024] Subsequently, step S4 is performed: the modified waxy rice powder is mixed with the main drug and other necessary excipients according to a predetermined ratio. The proportion of the modified waxy rice powder in the total mass of the tablet is 5% to 50%. For immediate-release tablets, the proportion is usually 10% to 25%; for sustained-release tablets, the proportion is increased to 30% to 50% in order to build a sufficient network structure; for traditional Chinese medicine extract tablets, the proportion is dynamically adjusted according to the water content of the extract, and is usually 20% to 40%. If the main drug is a traditional Chinese medicine extract with a water content of not less than 30%, the mass ratio of the main drug to the modified waxy rice powder is set to 1:0.5 to 1:2. The mixing process is carried out in a high-shear mixer, and the mixing time is 5 to 15 minutes, and the rotation speed is 200 to 600 revolutions per minute. In the initial stage of mixing, the speed is low to avoid dust flying; in the middle stage, the speed is increased to promote uniform dispersion; and in the final stage, the speed is reduced to exhaust air to eliminate agglomeration. The uniformity of mixing is verified by sampling and measuring the RSD value of the content of the main drug, and the RSD value is required to be less than 2%.

[0025] Finally, step S5 is performed: the mixed material is compressed into tablets by dry granulation, wet granulation or direct compression process. The process is selected according to the flowability and compressibility of the material. For formulations with good flowability, i.e. a rest angle of less than 40 degrees and no heat-sensitive main drug, direct compression is preferred to simplify the process and avoid solvent residues. For materials with poor flowability but good compressibility, dry granulation is used, and large tablets are formed by rolling and then granulated to improve flowability. For high-viscosity traditional Chinese medicine extract systems, wet granulation is used, and a small amount of purified water or ethanol is added as a wetting agent. After the granules with appropriate hardness are obtained, they are dried and compressed into tablets. The tablet compression process is completed on a rotary tablet press, and the die pressure is controlled at 5,000 to 15,000 Newton. The pressure feedback control system monitors the pressure value of each punch in real time. If the value deviates from the set value by more than ±500 Newton, the cam position is automatically adjusted to compensate for the deviation. The final tablet hardness is not less than 50 Newton, and the friability is less than 0.8%. The tablet appearance detection subsystem is running synchronously, and a high-resolution industrial camera is used to scan the edges, surface and side of the tablet. Based on the image gray gradient and texture feature recognition, defects such as cracked tablets, loose tablets, pits or color difference are identified, and unqualified products are separated by a pneumatic rejection device in real time.

[0026] The implementation of the above method relies on a complete application system. The system includes a raw waxy rice powder pretreatment unit, a modification unit, a post-treatment unit, a function determination module, a batching and mixing unit and a tablet compression and molding unit.

[0027] The raw waxy rice powder pretreatment unit is equipped with a vibrating feeder, a standard sieve and a near-infrared online detector. The raw waxy rice powder is fed into the sieve at a constant speed by the vibrating feeder, and particles larger than 100 microns are sieved out; the undersize material enters the detection channel, and the near-infrared spectrometer collects spectral data every second. The branched amylose content and moisture value are calculated by a pre-built calibration model. Only when both indicators meet the standards, the material is allowed to flow into the storage bin.

[0028] The modification processing unit contains five independent reaction chambers, corresponding to wet heat, acid hydrolysis, oxidation, cross-linking and enzyme catalytic modification processes respectively. Each chamber integrates temperature control system, pH electrode, stirring motor, metering pump and near-infrared probe. The temperature control system adopts double-loop design of electric heating jacket and cooling coil, with temperature control accuracy of plus or minus one degree; pH adjustment is achieved by injecting hydrochloric acid or sodium hydroxide solution through automatic titration pump; the stirring speed can be adjusted in the range of 50 to 300 revolutions per minute to ensure uniform reaction; the metering pump accurately controls the amount of reagent added, with an error of less than 0.5%. The parameters of each chamber are independently set and locked by the central controller to prevent process confusion caused by misoperation.

[0029] The post-processing unit is connected in turn with a fluidized bed dryer, a universal pulverizer and a vibrating sieve separator. The dryer is equipped with a humidity sensor and an exhaust frequency converter, which dynamically adjusts the air intake according to the outlet humidity; the pulverizer is provided with a current monitoring device, which automatically stops when the load current abnormally rises to prevent blockage; the sieve separator adopts a three-layer screen structure to simultaneously separate coarse powder, qualified powder and fine powder, only the qualified powder enters the finished product temporary storage tank.

[0030] The function determination module has a built-in database storing the performance parameter threshold matrix corresponding to the five types of modification processes. When the operator inputs the tablet type instruction (such as "immediate-release tablet", "sustained-release tablet" or "traditional Chinese medicine extract tablet"), the module automatically retrieves the matching process path and outputs the specification parameters of the target modified waxy rice flour, including the gelatinization temperature interval, peak viscosity range, water absorption swelling rate lower limit and disintegration time upper limit. The module also has a dynamic proportioning adjustment interface with the ingredient mixing unit. When the fluidity (determined by the angle of repose) or hygroscopicity (determined by the dynamic vapor sorption instrument) of the main drug exceeds the preset threshold, the system automatically increases the addition proportion of the modified waxy rice flour, which is not more than 50% of the total mass of the tablet, to ensure that the mixed material meets the tabletting process window.

[0031] The high-shear mixer of the ingredient mixing unit is equipped with a torque sensor and a temperature probe. The material resistance torque and temperature rise are monitored in real time during the mixing process, and if the temperature rise rate exceeds 2°C per minute, the stirring is automatically paused to prevent degradation of heat-sensitive ingredients. The mixing end point is confirmed by both the preset time and the torque stability double criteria.

[0032] The rotary tablet press of the tablet forming unit integrates a pressure closed-loop control system and a visual detection system. The pressure sensor is installed at the root of the upper and lower punch, with a sampling frequency of 1 kHz per second, and the data is used to adjust the output of the main drive servo motor in real time after filtering. The visual detection system uses a ring-shaped LED light source and a megapixel CMOS camera, and the image processing algorithm is based on morphological filtering and template matching, with a defect detection rate of not less than 99.5%.

[0033] In summary, the application gives the multifunctional integrated characteristics of waxy rice powder by precisely controlling the modification process parameters, and builds a matching intelligent application system, realizes the efficient, safe and low cost application of natural auxiliary materials in drug tablets. The method and system not only solve the molding problem of traditional Chinese medicine extract tablets, but also show better performance than traditional auxiliary materials in immediate-release and sustained-release preparations, and have significant industrialization value.

[0034] The above is only the preferred embodiment of the application, not to limit the protection scope of the application, therefore: all equivalent changes made according to the structure, shape, principle of the application should be covered within the protection scope of the application.

Claims

1. A method for applying modified glutinous rice flour in pharmaceutical tablets, characterized in that, include: Step S1: Obtain unmodified raw glutinous rice flour, and perform modification treatment on the raw glutinous rice flour. The raw glutinous rice flour has an amylopectin content of not less than 95%, a moisture content of not more than 10%, and a particle size D90 of not more than 100 micrometers. The modification treatment is selected from wet heat treatment, acid hydrolysis treatment, oxidation treatment, cross-linking treatment or enzyme catalytic modification treatment. Step S2: The modified glutinous rice flour is dried, pulverized and sieved to obtain the modified glutinous rice flour product. Step S3: Determine the functional role of the modified glutinous rice flour according to the type of the target drug tablet; Step S4: Mix the modified glutinous rice flour with the main drug and other necessary excipients in a preset ratio. The modified glutinous rice flour accounts for 5% to 50% of the total mass of the tablets. Step S5: The mixture is compressed into tablets using dry granulation, wet granulation, or direct tableting processes. The tableting pressure is controlled between 5,000 and 15,000 Newtons, the tablet hardness is not less than 50 Newtons, and the friability is less than 0.8%.

2. The method for applying the modified glutinous rice flour in pharmaceutical tablets according to claim 1, characterized in that, The modified glutinous rice flour is dried, pulverized, and sieved to obtain the finished modified glutinous rice flour product, including: The moisture content was reduced to below 3% by using a fluidized bed dryer at an inlet air temperature of 70 degrees Celsius for 30 minutes. Use a universal grinder to grind for five minutes at a speed of 3,000 revolutions per minute; The modified glutinous rice flour product is obtained by classifying the powder using a vibrating sieve with a D90 of 30 to 80 micrometers.

3. The method for applying the modified glutinous rice flour in pharmaceutical tablets according to claim 1, characterized in that, The functional role of the modified glutinous rice flour is determined according to the type of the target drug tablet, including: When the target tablet is an immediate-release tablet, modified glutinous rice flour obtained by wet heat treatment or acid hydrolysis is selected. Its structure is loose or porous, and it can quickly absorb water, swell and break when it comes into contact with water. Its disintegration time is controlled within five to twelve minutes. When the target tablet is a sustained-release tablet, modified glutinous rice flour obtained by cross-linking or oxidation treatment is selected. It forms a three-dimensional network skeleton to limit the rate of water penetration. Its dissolution rate in simulated intestinal fluid is not less than 70% within 24 hours and the disintegration time is greater than 30 minutes. When the target tablet is a traditional Chinese medicine extract tablet, modified glutinous rice flour obtained through enzyme catalytic modification is selected. Its viscosity index is between 80 and 120. It adsorbs free water and viscous polysaccharides in the traditional Chinese medicine extract, thereby reducing the overall viscosity of the material.

4. The method for applying the modified glutinous rice flour in pharmaceutical tablets according to claim 1, characterized in that, The modified glutinous rice flour is mixed with the main drug and other necessary excipients in a preset ratio, including: For immediate-release tablets, the modified glutinous rice flour addition ratio is 10% to 25%. For sustained-release tablets, the modified glutinous rice flour addition ratio is 30% to 50%. For Chinese herbal extract tablets, the proportion of modified glutinous rice flour added is 20% to 40%, and the main drug is a Chinese herbal extract with a water content of not less than 30%, and the mass ratio of the extract to the modified glutinous rice flour is 1:0.5 to 1:

2.

5. The method for applying the modified glutinous rice flour in pharmaceutical tablets according to claim 1, characterized in that, The mixture is compressed into tablets using dry granulation, wet granulation, or direct tableting processes, including: When the angle of repose of the mixture is less than 40 degrees and the active pharmaceutical ingredient is not heat-sensitive, direct compression shall be used. When the mixture has poor flowability but good compressibility, dry granulation is used; When the mixture is a high-viscosity traditional Chinese medicine extract system, wet granulation is used and purified water or ethanol is added as a wetting agent.

6. The method for applying the modified glutinous rice flour in pharmaceutical tablets according to claim 1, characterized in that: The modified glutinous rice flour product has a gelatinization initiation temperature of 60 to 80 degrees Celsius, a peak viscosity of 300 to 1500 centipoise, a water absorption swelling rate of not less than 200%, and a disintegration time of no more than 15 minutes in simulated gastric juice.

7. The method for applying the modified glutinous rice flour in pharmaceutical tablets according to claim 6, characterized in that: The gelatinization characteristics of the modified glutinous rice flour were determined using a rapid viscosity analyzer. The test conditions were: sample concentration of 10%, heating rate of 12 degrees Celsius per minute, heating from 50 degrees Celsius to 95 degrees Celsius and holding for 5 minutes, then cooling down to 50 degrees Celsius at the same rate. The peak viscosity, disintegration viscosity, and retrogradation value were recorded. The disintegration performance of the modified glutinous rice flour was determined using the disintegration time limit test method specified in Chinese Pharmacopoeia General Chapter 0921. The medium was 900 ml of artificial gastric fluid, and the temperature was maintained at 37 degrees Celsius ± 0.5 degrees Celsius. The time required for complete disintegration of all samples was recorded.

8. The method for applying the modified glutinous rice flour in pharmaceutical tablets according to claim 1, characterized in that, In step S1: the conditions for wet heat treatment are 75% to 85% relative humidity and 110°C to 130°C for 1 to 3 hours; the acidolysis treatment uses a hydrochloric acid solution with a concentration of 0.5% to 2% and reacts at a temperature of 40°C to 60°C for 30 to 120 minutes; the oxidation treatment uses a sodium hypochlorite solution with a concentration of 0.1% to 0.5% and reacts at a pH of 8.5 to 9.5 and a temperature of 30°C. The reaction is carried out at 50 degrees Celsius for one to two hours; the cross-linking treatment uses sodium trimetaphosphate as a cross-linking agent, with an amount of 0.3% to 1.5% of the dry weight of glutinous rice flour, and is carried out at pH 9 to 10 and a temperature of 45 to 55 degrees Celsius for two to four hours; the enzyme-catalyzed modification treatment uses pullulanase, with an enzyme addition amount of 0.1% to 0.5% of the dry weight of glutinous rice flour, and is carried out at pH 5.5 to 6.5 and a temperature of 55 to 65 degrees Celsius for four to eight hours.

9. A system for the application of modified glutinous rice flour in pharmaceutical tablets, characterized in that, include: The raw glutinous rice flour pretreatment unit is used to receive and screen raw glutinous rice flour that meets the requirements for amylopectin content, moisture content and particle size. The modified processing unit contains multiple independent reaction chambers, each equipped with temperature control, pH adjustment, stirring and feeding devices for performing wet heat treatment, acid hydrolysis treatment, oxidation treatment, cross-linking treatment or enzyme catalytic modification treatment. Each reaction chamber has an independent parameter control system. The post-processing unit includes a fluidized bed dryer, a universal pulverizer, and a vibrating screen, which are used to dry, pulverize, and classify the modified product to obtain a modified glutinous rice flour product with a D90 of 30 to 80 micrometers. The function determination module has a built-in database that stores the threshold values ​​of key performance parameters corresponding to different modification processes. This module automatically matches the optimal modification process path based on the input tablet type instruction and outputs the corresponding modified glutinous rice flour specification parameters. The ingredient mixing unit is equipped with a high-shear mixer for uniformly mixing the main drug, modified glutinous rice flour and other excipients according to the mass ratio. The tableting unit uses a rotary tablet press equipped with a pressure feedback control system to monitor and adjust the die pressure in real time, ensuring that the tablet hardness and brittleness meet the preset standards.

10. The system for applying modified glutinous rice flour in pharmaceutical tablets according to claim 9, characterized in that, Each reaction chamber in the modification unit is equipped with an online near-infrared spectroscopy monitoring module to collect real-time data on the changes in the molecular structure of glutinous rice flour during the reaction. The reaction is automatically terminated when the branch length distribution of amylopectin reaches the target range. A dynamic ratio adjustment interface is provided between the function determination module and the ingredient mixing unit. When the flowability or hygroscopicity of the active ingredient exceeds a preset threshold, the system automatically increases the proportion of modified glutinous rice flour added, up to a maximum of 50% of the total tablet mass. The tableting unit is equipped with a tablet appearance inspection subsystem, which uses a high-resolution industrial camera to scan the entire surface of the tablets, identify cracked tablets, loose tablets, pitted tablets, or color difference defects, and automatically reject unqualified products.

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